Gaucher's disease is the most common lysosomal storage disorder. The carrier frequency has been estimated to be as high as 1 in 12 among Ashkenazi Jews. In addition, because of the unique situation in which the same enzyme deficiency leads to both neurologic and non-neurologic disease, the disorder provides an unusual opportunity for the study of biochemical pathology and the metabolic basis of neurologic disease. More importantly, Gaucher's disease like many other inherited disorders is presently untreatable. The aim of these studies is to define the aberrant biochemistry in the group of disorders collected under the eponym of Gaucher's disease and to investigate methods of treating these disorders. As such, this disease serves as the prototype for this group of diseases. Results of these studies will be applicable to the whole group of lysosomal storage disorders. Studies of the enzymology and protein chemistry of the enzyme deficient in Gaucher's disease, as well as the cellular and molecular biology and genetics will contribute significantly to construction of therapeutic modalities. The clinical disease will be studied by the most current methods. Enzyme and gene replacement will be studied as potential approaches to treatment. The goal of this proposal is to apply basic scientific data to the treatment of this disorder.